The immunologic disorders, idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE) neonatal (INT)-post-transfusion (PTP)- and drug-purpura account for the majority of clinical thrombocytopenias. The immune reactions involved in these disorders are relevant to understanding autoimmunity, histocompatibility, malignant surveillance, isoimmune reactions interfering with support of chemotherapy and cellular immune injury generally. We have developed more precise and sensitive tests for cell-associated IgG, IgM, IgA and albumin and found that immune injury by specific antibody causes platelets to associate with nonspecific Ig's and albumin. By electronmicroscopy this association appears to result from trapping of plasma protein by cytoplasmic-free platelet membranes rather than by association of Ig's with Fc receptor. An animal model for ITP was developed that duplicated the cellular and immunologic abnormalities of this disease. Platelet immune abnormalities of SLE were found to differ from those of ITP in that cell-associated Ig's appeared to be due to immune complexes rather than nonspecific entrapment of plasma. Four cases of PTP were found to be due to isoantibodies to previously unrecognized platelet antigen specificities; we have extensively determined the molecular characteristics of one of these determinants. We have developed an intracellulose transfer technique to separate platelet membrane proteins that permits detecting antiplatelet antibodies of INT and PTP more sensitively and specifically than previously possible. Methods were developed to purify platelet membrane glycoproteins to obtain large amounts for clinical diagnostic tests.